A new effort concentrating on animal models of AIDS was undertaken in August, 1987. Two model systems were established: (1) a primate model using the various simian immunodeficiency viruses (SIV); and (2) a feline model using the feline immunodeficiency virus (FIV). These viruses belong to the lentivirus subfamily of retroviruses and induce chronic persistent infection and immunodeficiency viruses (HIV-1 and HIV-2), while FIV is much less closely related to human or primate viruses based on lack of antigenic cross-reactivity and limited sequence homology. Challenge pools of FIV and several SIVs have been prepared and are undergoing infectivity titration in animals. Disease (simian AIDS) has been produced by SIV and cats have been infected by FIV, but to date minimal disease has been detected. Both FIVs and SIVs have been cloned and sequenced and their sequences compared with those of other related lentiviruses. Genetic drift of SIV over a 12 month interval was documented in monkeys experimentally infected with a molecular clone of SIVsm. Significant variation was detected in the envelope glycoprotein gene but not in the integrase gene. SIV isolates from healthy infected monkeys accumulated multiple in-frame stop codons in the env gene, whereas isolates from immunodeficient animals did not have such mutations. An inactivated SIV vaccine prepared by psoralen/UV treatment induced SIV envelope glycoprotein antibodies after a single inoculation. Significant sequence diversity in the env gene was detected among FIV isolates from different geographic locations. Also, serologic evidence of infection with FIV was detected with high frequency among free-ranging, wild caught felids such as Florida panthers (Felis concolor).